X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation
| Autor: | Synofzik, Matthis, Müller vom Hagen, Jennifer, Haack, Tobias B, Wilhelm, Christian, Lindig, Tobias, Beck-Wödl, Stefanie, Nabuurs, Sander B, van Kuilenburg, André BP, de Brouwer, Arjan PM, Schöls, Ludger |
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| Přispěvatelé: | Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, Laboratory Genetic Metabolic Diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male genetics [Hearing Loss] PRPS1 protein human Molecular Sequence Data chemistry [Ribose-Phosphate Pyrophosphokinase] Deaf-Blind Disorders Charcot-Marie-Tooth Disease genetics [Genetic Diseases X-Linked] Genetics Ribose-Phosphate Pyrophosphokinase Animals Humans Genetics(clinical) Pharmacology (medical) Optic atrophy ddc:610 Amino Acid Sequence Medicine(all) Sequence Homology Amino Acid Research genetics [Deaf-Blind Disorders] Genetic Diseases X-Linked Hearing loss genetics [Ataxia] Pedigree Early onset ataxia Mutation Behr syndrome Ataxia Female genetics [Ribose-Phosphate Pyrophosphokinase] genetics [Charcot-Marie-Tooth Disease] |
| Zdroj: | Orphanet journal of rare diseases 9(1), 24 (2014). doi:10.1186/1750-1172-9-24 Orphanet Journal of Rare Diseases Orphanet journal of rare diseases, 9(1). BioMed Central Orphanet Journal of Rare Diseases; Vol 9 |
| ISSN: | 1750-1172 |
| DOI: | 10.1186/1750-1172-9-24 |
| Popis: | Background X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1. As only few families have been described, knowledge about the relation between these syndromes, the phenotypic spectrum in patients and female carriers, and the relation to underlying PRS-I activity is limited. Methods We investigated a family with a novel PRPS1 mutation (c.830A > C, p.Gln277Pro) by extensive phenotyping, MRI, and genetic and enzymatic tests. Results The male index subject presented with an overlap of CMTX5 and Arts syndrome features, whereas his sister presented with prelingual DFN2. Both showed mild parietal and cerebellar atrophy on MRI. Enzymatically, PRS-I activity was undetectable in the index subject, reduced in his less affected sister, and normal in his unaffected mother. Conclusions Our findings demonstrate that CMTX5, Arts syndrome and DFN2 are phenotypic clusters on an intrafamilial continuum, including overlapping phenotypes even within individuals. The respective phenotypic presentation seems to be determined by the exact PRPS1 mutation and the residual enzyme activity, the latter being largely influenced by the degree of skewed X-inactivation. Finally, our findings show that brain atrophy might be more common in PRPS1-disorders than previously thought. |
| Databáze: | OpenAIRE |
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